POS0606 HOW DO GLUCOCORTICOIDS, BIOLOGIC DISEASE-MODIFYING ANTI-RHEUMATIC DRUGS AND DISEASE ACTIVITY IMPACT THE RISK OF STAPHYLOCOCCUS AUREUS BACTEREMIA IN RHEUMATOID ARTHRITIS PATIENTS? A NATIONWIDE NESTED CASE CONTROL STUDY IN THE DANISH DANBIO COHORT
Authors: S. Dieperink, B. Glintborg, F. Mehnert, M. Nørgaard, T. Benfield, C. Torp-Pedersen, L. B. Oestergaard, A. Petersen, M. L. Hetland
Journal: Annals of the Rheumatic Diseases (2022)

Background Staphylococcus aureus bacteremia (SAB) has high mortality and rheumatoid arthritis (RA) patients are at increased risk,[1] however, the role of anti-rheumatic treatments and disease activity is unclear.[2,3] Objectives To explore the impact of treatment with glucocorticoids and biologic disease-modifying anti-rheumatic drugs (bDMARDs) and disease activity on the risk of SAB in RA patients. Methods Nested case control study in a nationwide cohort of RA patients (DANBIO) with no history of SAB. Cases had a first-time microbiologically verified SAB between 2010-2018. Controls were incidence density matched (age and sex) at time of SAB (index date). We linked data from DANBIO (e.g. disease activity, anti-rheumatic treatment) to other national registries (comorbidities, prescriptions, socioeconomic status, etc). Treatments were redeemed prescriptions or registrations in DANBIO (oral glucocorticoids, bDMARDs) 0-2 years before the index date. Dose of oral glucocorticoids was retrieved from either DANBIO or estimated from the latest prescription. Risk associated with treatment and disease activity was assessed by multivariate conditional logistic regression. For treatments, excess cases/10,000 exposed/year were calculated by multiplying the fully adjusted OR (95%CI) with the incidence rate in the cohort. Missing data was handled by multiple imputation. Results We identified 180 cases in 30,479 RA patients (IR 106.7/100,000 person-years) and matched 720 controls (53% women, median age 73 years, IQR 65;80). For cases, orthopedic implants were frequent (53%/34% for cases/controls), many had recent surgery (38%/5%), longstanding RA (13 years (6;21)/8 (4;14)), joint erosions (48%/39%), moderate (29%/16%) or high (10%/7%) disease activity, and used glucocorticoids (41%/19%) and bDMARDs (31%/20%). Adjusted ORs were high for current use of oral glucocorticoids, especially for doses &gt;10mg/day (OR=14.5 (4.0; 52.2)). For bDMARDs, adjusted OR was 1.9 (1.1; 3.2). Correspondingly, the treatments increased risk with 144 and 9 excess cases/10,000/year, respectively (Table 1). For disease activity, adjusted ORs were &gt;1 (non-significant) for moderate and high disease activity compared with remission (Figure 1). Figure 1. Disease activity and risk of Staphylococcus aureus bacteremia Table 1. Use of oral glucocorticoids and biologic disease-modifying anti-rheumatic drugs (bDMARDs) 0-2 years before the index date and risk of Staphylococcus aureus bacteremia (SAB) SAB cases,n=180 Controls, n=720 OR (95% CI) * Number of excess cases/10,000 exposed/year (confidence limits) Glucocorticoids n (%) n (%) No 67 (37) 450 (63) ref Yes 113 (63) 270 (38) 2.4 (1.5; 3.8 ) 15 (6; 30) Former user a 39 (22) 133 (19) 1.7 (0.9; 3.0) NA Current user b 74 (41) 137 (19) 3.2 (1.9; 5.3 ) 23 (9; 46) Current daily dose &gt;0-5 mg 44 (24) 108 (15) 2.1 (1.1; 3.8 ) 11 (1; 30) &gt;5-10mg 18 (10) 26 (4) 3.5 (1.4; 8.6 ) 26 (4; 81) &gt;10mg 12 (7) 8 (1) 14.5 (4.0; 52.2 ) 144 (32; 46) bDMARDs No 111 (62) 558 (78) ref Yes 69 (38) 162 (23) 1.9 (1.1; 3.2 ) 10 (1; 24) Former user a 14 (8) 18 (3) 2.1 (0.8; 5.8) NA Current user b 55 (31) 144 (20) 1.9 (1.1; 3.2 ) 9 (1; 23) a &gt;3 to 24 months before (rituximab &gt;12 to 24 months), b 0-3 months before (rituximab 0-12 months) * adjusted for sex, age, comorbidities, implants, recent surgery, RA disease duration, time since entry, csDMARDs, socioeconomic-, sero-, erosive-, functional- and smoking status, body mass index, and disease activity (high/low/moderate/remission) Conclusion Oral glucocorticoids and bDMARDs increased relative risk of SAB, with number of excess cases being high for oral glucocorticoids (&gt;10 mg/day) and low for bDMARDs. Disease activity had minor impact on the risk. This emphasizes that high dose glucocorticoids should be used with caution. References [ 1] Dieperink SS, resubmitted after revision Jan 2022 [2]Smit J et al. 2016 doi:10.1016/j.mayocp.2016.04.023 [3]Sams M et al. 2015 doi:10.1007/s00296-015-3239-8 Acknowledgements We wish to acknowledge the valuable inputs from patient representative Pia Lüchau Pedersen who participated in the initial brainstorming phase that led to the hypotheses being tested in this study Disclosure of Interests None declared